D. Casanova

Safety, tolerability and potential efficacy of injection of autologous adipose-derived stromal vascular fraction in the fingers of patients with systemic sclerosis: an open-label phase I trial

Background In patients with systemic sclerosis (scleroderma, SSc), impaired hand function greatly contributes to disability and reduced quality of life, and is insufficiently relieved by currently available therapies. Adipose tissue-derived stromal vascular fraction (SVF) is increasingly recognised as an easily accessible source of regenerative cells with therapeutic potential in ischaemic or autoimmune diseases. We aimed to measure for the first time the safety, tolerability and potential efficacy of autologous SVF cells local injections in patients with SSc with hand disability. Methods We did an open-label, single arm, at one study site with 6-month follow-up among 12 female SSc patients with Cochin Hand Function Scale score >20/90. Autologous SVF was obtained from lipoaspirates, using an automated processing system, and subsequently injected into the subcutaneous tissue of each finger in contact with neurovascular pedicles. Primary outcome was the number and the severity of adverse events related to SVF-based therapy. Secondary endpoints were changes in hand disability and fibrosis, vascular manifestations, pain and quality of life from baseline to 2 and 6 months after cell therapy. Findings All enrolled patients had surgery, and there were no dropouts or patients lost to follow-up. No severe adverse events occurred during the procedure and follow-up. Four minor adverse events were reported and resolved spontaneously. A significant improvement in hand disability and pain, Raynauds phenomenon, finger oedema and quality of life was observed. Interpretation This study outlines the safety of the autologous SVF cells injection in the hands of patients with SSc. Preliminary assessments at 6 months suggest potential efficacy needing confirmation in a randomised placebo-controlled trial on a larger population. Funding GFRS (Groupe Francophone de Recherche sur la Sclérodermie). Clinical Trials number NCT01813279.

Comparison of five dermal substitutes in full-thickness skin wound healing in a porcine model.

The wound healing attributes of five acellular dermal skin substitutes were compared, in a two-step procedure, in a porcine model. Ten pigs were included in this experimental and randomized study. During the first step, dermal substitutes (Integra(®), ProDerm(®), Renoskin(®), Matriderm(®) 2mm and Hyalomatrix(®) PA) were implanted into full-thickness skin wounds and the epidermis was reconstructed during a second step procedure at day 21 using autologous split-thickness skin graft or cultured epithelial autograft. Seven pigs were followed-up for 2 months and 3 pigs for 6 months. Dermal substitute incorporation, epidermal graft takes, wound contraction and Vancouver scale were assessed, and histological study of the wounds was performed. Results showed significant differences between groups in dermis incorporation and in early wound contraction, but there was no difference in wound contraction and in Vancouver scale after 2 and 6 months of healing. We conclude there was no long-term difference of scar qualities in our study between the different artificial dermis. More, there was no difference between artificial dermis and the control group. This study makes us ask questions about the benefit of artificial dermis used in a two-step procedure.

Management of wounds of exposed or infected knee prostheses

Skin damage after total knee arthroplasty may jeopardise the functional benefit of the prosthesis. In such cases standard treatment is aimed at avoiding arthrodesis, sometimes replacing the implant and, in exceptional cases, amputation. In most cases early and adequate coverage of the soft tissue defect may make it possible to salvage the prosthesis. Ten patients with skin damage after total knee arthroplasty were treated by debridement of the wound, which was then covered with a pedicled gastrocnemius muscle flap. This was supported by local irrigation and systemic antibiotics. Seven patients were reviewed after a mean follow-up of 28 months (range 14-59). Six patients kept their prostheses and one had a relapse caused by infection at 22 months, which required removal of the prosthesis and secondary arthrodesis. The gastrocnemius muscle flap provides good quality coverage, permits early mobilisation and fast rehabilitation, and reduces the rate of arthrodesis after failure of total knee arthroplasty.Skin damage after total knee arthroplasty may jeopardise the functional benefit of the prosthesis. In such cases standard treatment is aimed at avoiding arthrodesis, sometimes replacing the implant and, in exceptional cases, amputation. In most cases early and adequate coverage of the soft tissue defect may make it possible to salvage the prosthesis. Ten patients with skin damage after total knee arthroplasty were treated by debridement of the wound, which was then covered with a pedicled gastrocnemius muscle flap. This was supported by local irrigation and systemic antibiotics. Seven patients were reviewed after a mean follow-up of 28 months (range 14-59). Six patients kept their prostheses and one had a relapse caused by infection at 22 months, which required removal of the prosthesis and secondary arthrodesis. The gastrocnemius muscle flap provides good quality coverage, permits early mobilisation and fast rehabilitation, and reduces the rate of arthrodesis after failure of total knee arthroplasty.

Autologous adipose-derived stromal vascular fraction in patients with systemic sclerosis: 12-month follow-up

OBJECTIVE Impaired hand function greatly contributes to disability and reduced quality of life in SSc patients. Autologous adipose-derived stromal vascular fraction (ADSVF) is recognized as an easily accessible source of regenerative cells. We reported positive 6-month safety and efficacy results from an open-label clinical trial assessing s.c. injection of autologous ADSVF into the fingers in SSc patients. The objective of this report is to describe the effects at 12 months. METHODS Twelve females, mean age 54.5 years (s.d. 10.3), were assessed 1 year after ADSVF injection. Patients were eligible if they had a Cochin Hand Function Scale score >20/90. ADSVF was obtained from lipoaspirate using an automated processing system and subsequently injected into the s.c. tissue of each finger in contact with neurovascular pedicles in a one-time procedure. Endpoints were changes in hand disability and skin fibrosis, vascular manifestations, pain and quality of life at the 12 month follow-up. During the visit, patients estimated the benefit of the procedure with a specific self-completed questionnaire. RESULTS A significant decrease from baseline of 51.3% (P < 0.001) for Cochin Hand Function Scale score, 63.2% (P < 0.001) for RP severity and 46.8% (P = 0.001) for quality of life (Scleroderma Health Assessment Questionnaire) was observed. A significant improvement of finger oedema, skin sclerosis, motion and strength of the hands and of the vascular suppression score was also noted. The reduction in hand pain approached statistical significance (P = 0.052). The questionnaire revealed a benefit in daily activities, housework and social activities. CONCLUSION ADSVF injection is a promising therapy and appears to have benefits that extend for at least 1 year.

The microbial epidemiology of breast implant infections in a regional referral centre for plastic and reconstructive surgery in the south of France

BACKGROUND Breast implant infections are usually caused by Staphylococcus aureus and coagulase-negative staphylococci. Gram-negative bacilli are rarely reported to be involved in breast implant infections. METHODS Thirty-seven cases of microbiologically confirmed breast implant infection managed from January 2008 to June 2012 in the study centre were reviewed, including 10 cases from the study centre itself and 27 cases from private clinics in the region. RESULTS The prevalence of breast implant infection in the study centre was 0.74% of breast implantation, i.e., 3.23% in breast reconstruction for breast cancer and 0.27% in aesthetic breast augmentation (p=0.0002). Of the 37 cases, 30% had undergone radiotherapy and 11% had undergone a lymph node dissection. S. aureus was identified in 18 cases, Gram-negative bacilli in 10 cases, coagulase-negative staphylococci in eight cases, anaerobic bacteria in eight cases, and streptococci in three cases. Pseudomonas aeruginosa was the second most commonly identified pathogen. Staphylococcus epidermidis was the most frequent coagulase-negative Staphylococcus species. In addition to Propionibacterium acnes and Actinomyces neuii, other facultative and strict anaerobic bacteria have not been reported before, e.g., Bacteroides thetaiotaomicron, Corynebacterium simulans, Dermabacter hominis, Finegoldia magna, and Peptoniphilus harei. Seventy-percent of cases were treated by immediate implant removal. All cases treated only with antibiotics were treated with surgery at the second visit. CONCLUSIONS The microbiological epidemiology was noted by an increasing the proportion of Gram-negative bacteria and anaerobic bacteria detected with the advent of MALDI-TOF MS and molecular identification for diagnosis.

New fat-derived products for treating skin-induced lesions of scleroderma in nude mice

IntroductionScleroderma is characterized by cutaneous manifestations that mainly affect the hands, arms and face. As of today, there is no treatment for fibrotic skin lesions of scleroderma. Previously we generated and validated a model of scleroderma-like skin sclerosis in nude mice, appropriate to inject human derived products. We showed that the subcutaneous injection of micro-fat (MF), purified and injected using small caliber cannulas, have anti-fibrotic and pro-angiogenic effects and appears more suitable for the treatment of skin lesions of scleroderma compared to the gold standard (Coleman’s technique or macro-fat). Here we compared the long-term efficacy of micro-fat “enriched” with other therapeutic products including the stromal vascular fraction (SVF) of fat and platelet-rich plasma (PRP) from blood in our murine model of scleroderma.MethodsWe used 72 nude mice in this study. We formed six experimental groups: Macro-fat, MF, SVF, PRP, MF + SVF, MF + PRP. This project has three phases: i) Induction of skin sclerosis by daily subcutaneous injections of bleomycin (BLM) for 4 weeks in nude mice; ii) Purification and injection of the different cell therapy products; iii) Histological analyses done 8 weeks post-injections.ResultsMF + SVF and MF + PRP significantly reversed dermal and epidermal sclerosis (P <0.01). Macro-fat, SVF, PRP only corrected the dermal sclerosis (P <0.05). Epidermal sclerosis was reduced in treatments containing MF (P <0.01). MF was more stable. Products containing the SVF were associated with a significant increase of the local vascularization (P <0.01).ConclusionsAll tested substances were effective in treating skin-induced lesions of scleroderma with different levels of fibrosis and vascular improvement; MF derived products are more stable and SVF demonstrated better pro-angiogenic effects. The observed efficacy of this combination of products in the animal model provides a rationale for potential clinical applications to treat human disease.

Long-term follow-up after autologous adipose-derived stromal vascular fraction injection into fingers in systemic sclerosis patients

INTRODUCTION Hand involvement confers a substantial handicap in work and daily activities in patients with Systemic sclerosis (SSc). Autologous adipose-derived stromal vascular fraction is as an easily accessible source of cells with regenerative effects. We previously performed a phase I open-label clinical trial (NTC01813279) assessing the safety of subcutaneous injection of autologous adipose-derived stromal vascular fraction. Six and 12-month data have been reported. As patients were followed in our medical centre, we report their longer-term outcome beyond the end of the trial. PATIENTS AND METHOD Twelve females, mean age 54.5±10.3 years, initially enrolled in the clinical trial were assessed during a scheduled medical care, which took place between 22 and 30months after treatment. RESULTS Multiple patient-reported outcomes showed sustained improvement, in comparison with the assessment performed just before surgery: 62.5% in the Cochin Hand Function Scale, 51.1% in the Scleroderma Health Assessment Questionnaire, 33.1% in hand pain, and 88.3% in the Raynaud Condition Score. A decrease in the number of digital ulcers number was noted. Mobility, strength and fibrosis of the hand also showed improvement. None of the 8 patients who had previously received iloprost infusion required new infusion. CONCLUSION Despite the limits of an open label study, the data are in favour of the long-term safety of the adipose-derived stromal vascular fraction injection. Two randomized double blind, placebo-controlled trials of this therapeutic agent are ongoing in the USA (NCT02396238) and in France (NCT02558543) and will help determine the place of this innovative therapy for SSc patients.

Efficacy of Autologous Microfat Graft on Facial Handicap in Systemic Sclerosis Patients

Background: Autologous adipose tissue injection is used in plastic surgery for correction of localized tissue atrophy and has also been successfully offered for treatment of localized scleroderma. We aimed to evaluate whether patients with systemic sclerosis (SSc) and facial handicap could also benefit from this therapy. Methods: We included 14 patients (mean age of 53.8 ± 9.6 years) suffering from SSc with facial handicap defined by Mouth Handicap in Systemic Sclerosis Scale (MHISS) score more than or equal to 20, a Rodnan skin score on the face more than or equal to 1, and maximal mouth opening of less than 55 mm. Autologous adipose tissue injection was performed under local anesthesia using the technique of subcutaneous microinjection. The main objective of this study was an improvement of the MHISS score 6 months after the surgical treatment. Results: The procedure was well tolerated. We observed a mean decrease in the MHISS score of 10.7 points (±5.1; P < 0.0001) at 6 months (35% improvement). Secondary efficacy parameters assessing perioral skin sclerosis, maximum mouth opening, sicca syndrome, and facial pain significantly improved at 3 and 6 months postsurgery. At a 6-month follow-up, 75% of patients were satisfied or very satisfied of the adipose tissue microinjection therapy. Conclusions: Our study suggests that subcutaneous perioral microfat injection in patients with SSc is beneficial in the treatment of facial handicap, skin sclerosis, mouth opening limitation, sicca syndrome, and facial pain. Thus, this minimally invasive approach offers a new hope for face therapy for patients with SSc.

Osteomyelitis of sternum and rib after breast prosthesis implantation: A rare or underestimated infection?

Sternum and rib osteomyelitis complicated from breast implant infection is rare. We report a case of early sternum and rib osteomyelitis occurred during breast implant infection managed in an inter-regional referral center for bone/joint infections in the south of France.

Auguste Lumière, pionnier de la cicatrisation moderne

Resume Le 28 decembre 1895 Louis et Auguste Lumiere font decouvrir au public du « Grand Cafe » a Paris une invention qui va revolutionner l’image : le cinematographe. Alors que Louis poursuit ses travaux sur l’image et invente les plaques autochromes pour la photographie couleur, Auguste s’oriente vers la biologie et la medecine. Depuis Ambroise Pare peu de medecins se sont interesses a la cicatrisation. Carrel et Lecomte du Nouy effectuent les premieres etudes au debut du XX e siecle mais Auguste Lumiere sera pionnier dans l’etude et le traitement moderne des plaies. Il applique les principes de la medecine experimentale. Il etudie sur 44 chiens la vitesse et la qualite de la cicatrisation dans des conditions generales et locales definies. Durant l’hiver 1914–1915 il etudie a l’Hotel-Dieu de Lyon plusieurs centaines de plaies chez les blesses de guerre. Il etablit des regles de cicatrisation normale qu’il publie en 1922. Dans le service du Pr Leon Berard il est choque par la fetidite des salles ou les pansements secs sont renouveles une fois par semaine. Il va mettre au point en 1915 un « pansement-traitement » revolutionnaire, sterilise a l’autoclave, a base de gazes a mailles de 2 mm impregnees de vaseline et de baume de Perou : le Tulle Gras ® . Il s’attache a la desinfection des plaies avec un desinfectant iode pulverise en fines gouttelettes. Auguste et Louis Lumiere eurent une vie feconde de projets, d’inventions et lorsqu’Auguste decede en 1954 il aura depose plus d’une centaine de brevets.